Yuping Suo

Suppressor of cytokine signaling 6 (SOCS6) mediates ubiquitination degradation of SLC7A11 to drive ferroptosis and block lipid metabolism in ovarian cancer cells

Ovarian cancer (OVCA) is a highly malignant gynecological tumor characterized by a dismal 5-year survival rate that is closely linked to aberrant ferroptosis regulation and lipid metabolic reprogramming. This study integrated bioinformatics analyses of TCGA and The Human Protein Atlas datasets, clinical validation in 30 pairs of OVCA tissues, in vitro functional assays using HO8910 and HEYT30 cell lines, and nude mouse xenograft models to explore the role of suppressor of cytokine signaling 6 (SOCS6) in OVCA prognosis. The results revealed that SOCS6 was significantly downregulated in OVCA tissues and cell lines, and low expression was strongly correlated with poor patient prognosis. Mechanistically, SOCS6 overexpression inhibited cellular proliferation, migration, and invasion and enhanced sensitivity to the ferroptosis inducer erastin. This effect occurs by promoting the ubiquitin-proteasomal degradation of the ferroptosis antagonist SLC7A11, reducing intracellular glutathione (GSH) levels, and augmenting reactive oxygen species (ROS) and Fe

DDIAS promotes endometrial cancer progression via β-catenin signaling

Background DDIAS has been recognized as an oncogene in various cancers, but its role in endometrial cancer remains unexplored. Methods The expression of DDIAS in normal endometrium and endometrial cancer samples was analysed via the The Cancer Genome Atlas (TCGA) database, and prognostic analysis was performed. The differential expression of DDIAS between endometrial cancer and normal endometrium tissues was analyzed using quantitative polymerase chain reaction (qPCR). To study the expression of DDIAS in endometrial cancer, immunohistochemistry was performed on endometrial cancer, atypical endometrial hyperplasia and normal endometrial tissue. The association between DDIAS expression and clinicopathology was analysed. The expression of DDIAS in endometrial cancer cell lines was studied via Western blot (WB) analysis. DDIAS was knocked down in endometrial cancer cell lines via small interfering RNA (siRNA), and the effects of DDIAS knockdown on endometrial cancer cell biology and its related regulatory mechanisms were investigated via Cell Counting Kit-8(CCK8), Colony formation assay, scratch test, Transwell, and WB assays. Finally, the relevant regulatory mechanisms were verified using rescue experiments. Results According to the public database analysis, High DDIAS expression correlates with endometrial cancer and predicts unfavorable prognosis..The qPCR confirmed higher expression of DDIAS in tumor samples.We found that DDIAS was highly expressed in endometrial cancer and atypical endometrial hyperplasia, and that the upregulation of DDIAS expression predicted poor prognosis. In endometrial cancer, higher DDIAS expression was associated with increased tumor grade and advanced FIGO stage. In terms of cellular function, knocking down DDIAS suppressed the proliferation, migration and invasion capabilities of endometrial cancer cells. In the mechanistic pathway, reducing DDIAS expression led to the inhibition of β-catenin and its downstream targets, including c-Myc, cyclin D1, and survivin, while also suppressing epithelial-mesenchymal transition (EMT).However, these changes were rescued by the upregulation of β-catenin. Conclusion DDIAS regulated EMT in endometrial cancer cell migration and invasion through the β-catenin pathway, demonstrating that DDIAS is a potential target for the treatment of endometrial cancer.

Porphin e6 complex loaded with gold nanorod mesoporous silica enhances photodynamic therapy in ovarian cancer cells in vitro

A growing amount of experimental evidence has proven that the application of gold nanorods (AuNRs) in photodynamic therapy (PDT) can significantly enhance its therapeutic efficacy. The aim of this study was to establish a protocol for investigating the effect of gold nanorods loaded with the photosensitizer chlorin e6 (Ce6) on photodynamic therapy in the OVCAR3 human ovarian cancer cell line in vitro and to determine whether the PDT effect was different from that of Ce6 alone. OVCAR3 cells were randomly divided into three groups: the control group, Ce6-PDT group, and AuNRs@SiO

Study on the mechanism of photodynamic therapy mediated by 5-aminoketovalerate in human ovarian cancer cell line

We aimed to investigate the mechanism and effect of photodynamic treatment mediated by 5-aminoketovalerate (5-ALA-PDT) on human ovarian cancer cells (OVCAR3 cells) and to provide a theoretical basis for the subsequent experimental step in vivo. Human ovarian cancer OVCAR3 cells were randomly divided into four groups: control group, laser irradiation alone group, photosensitizer alone group, and photodynamic treatment group. Alterations in cell morphology were observed with an inverted light microscope; cell viability was examined by CCK-8 assays. The ROS content and apoptosis rate were examined by flow cytometry analysis. Western blot was used to detect the expression of apoptosis-related proteins, such as caspase-3, Bax, and Bcl-2, and the expression of cleaved caspase-3 in live cells was detected by a cleaved caspase-3 assay kit. Inverted light microscopy showed alterations in cell morphology in different stages. Comparison with the three other groups indicated that tumor cell proliferation was significantly decreased in the photodynamic treatment group (P < 0.05). Flow cytometry analysis revealed that the content of ROS was higher in the photodynamic group than in the other three groups, and the apoptosis rate was higher in the photodynamic treatment group. The difference compared with the other three groups was statistically significant (P < 0.001). The western blot results indicated that the protein expression of Bcl-2 and caspase-3 was decreased in the photodynamic treatment group, and the protein expression level of Bax was increased (P < 0.05). The expression of cleaved caspase-3 was increased in the photodynamic treatment group compared with the other groups according to the data obtained with a microplate reader. Thus, our results demonstrated that the apoptosis and viability of OVCAR3 cells are altered in response to 5-ALA-PDT; however, no remarkable effects were observed in ovarian cancer cells treated with laser irradiation or photosensitizer alone. 5-ALA-PDT can significantly inhibit the growth of human ovarian cancer cells, and the mechanism of this effect is related to the tumor cell apoptosis mediated by the downregulation of Bcl-2 and caspase-3 and upregulation of Bax protein expression.

MAP7 interacts with RC3H1 and cooperatively regulate cell-cycle progression of cervical cancer cells via activating the NF-κB signaling

Ensconsin is encoded by the MAP7 gene and belongs to the microtubule-associated proteins. This study aimed to explore its functional roles and partners in cell-cycle progression in cervical cancer. Data from the Cancer Genome Atlas-Cervical & Endocervical Cancer (TCGA-CESC) and the Genotype-Tissue Expression project were used for bioinformatic analysis. SiHa cells were used for in-vitro and in-vivo analysis. Co-immunoprecipitation (Co-IP) assay was conducted to explore the proteins interacted with MAP7. Results showed that MAP7 mRNA expression might serve as an independent biomarker of shorter survival. MAP7 overexpression elevated cyclin D1/cyclin B1 expression, facilitated cell-cycle progression and promoted SiHa cell growth in a xenograft tumor model. Co-IP experiments confirmed a novel interaction between MAP7 and RC3H1. Knockdown of either RC3H1 or MAP7 significantly attenuated cyclin D1/cyclin B1 upregulation, and cell-cycle progression induced by the other partner. MAP7 overexpression led to increased expression of P-IKK (Ser176/177) and P-p65 (Ser536). RC3H1 inhibition abrogated MAP7 induced upregulation of P-IKK and P-p65. Data in TCGA-CESC showed that MAP7 expression was positively correlated with its copy number segments, but was negatively correlated with the methylation level of three CpG sites within the gene locus. Demethylation treatment by 5-Aza-dC elevated both MAP7 mRNA and protein expression in a dose-dependent manner. In conclusion, this study revealed a novel interaction between MAP7 and RC3H1 in cervical cancer cells, which cooperatively enhanced cyclin D1/cyclin B1 expression and facilitated cell-cycle progression. These effects were at least partly mediated by activated canonical IKK/NF-kB signaling.